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Trial record 27 of 43 for:    CAH

Comparison of Chronocort® With Standard Glucocorticoid Therapy in Patients With Congenital Adrenal Hyperplasia

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ClinicalTrials.gov Identifier: NCT02716818
Recruitment Status : Recruiting
First Posted : March 23, 2016
Last Update Posted : July 17, 2017
Sponsor:
Information provided by (Responsible Party):
Diurnal Limited

Brief Summary:
This study is a parallel arm, randomised, open-label study, including dose titration and admissions for four overnight stays for 24-hour endocrine profiles. It will compare the efficacy, safety and tolerability of Chronocort® with standard glucocorticoid replacement therapy in the treatment of congenital adrenal hyperplasia (CAH) over a treatment period of 6 months. Dose titration decisions in both treatment groups will be made by a central independent physician, blinded to the treatment arm, using information generated from the 24-hour endocrine profiles. Each treatment arm will be subject to the same titration rules throughout the study, ensuring that opportunities for optimisation and control of androgens are the same in both groups.

Condition or disease Intervention/treatment Phase
Congenital Adrenal Hyperplasia Drug: Chronocort® Drug: standard glucocorticoid therapy Phase 3

Detailed Description:

At baseline, subjects will be admitted overnight for a 24-hour endocrine profile whilst on their standard therapy. Subjects will attend the study site in the morning and have 17-hydroxyprogesterone (17-OHP) and androstenedione (A4) levels assessed at 15:00, 17:00, 19:00, 21:00, 23:00, 01:00, 03:00, 05:00, 07:00, 09:00, 11:00, 13:00 and 15:00. Safety laboratory tests, a DEXA scan for body composition, and height, weight and waist circumference will be recorded. Subjects will then be randomised to Chronocort® or to continue on their standard care. Randomisation will be stratified by baseline treatment:

  1. hydrocortisone only or
  2. prednisone or prednisolone, alone or in combination with hydrocortisone
  3. dexamethasone only or in combination with any other glucorticoid

The initial dose setting at the start of the Chronocort® treatment will be based on hydrocortisone dose equivalent of baseline therapy in accordance with standard clinical practice. Further dose refinement/titration will be conducted in both treatment groups as necessary after 4 weeks and 12 weeks using a standardised titration algorithm after the subject has been re-admitted for further 24-hour endocrine profiles. Safety endpoints will also be measured at the 07:00 morning sample of each 24-hour profile assessment day. The decision to change doses in both treatment groups will be made by a central independent blinded physician, with the actual change in dose then being made by the local investigator looking after the subject. At 6 months, all the baseline tests will be repeated (including the 24-hour profile). All subjects may then continue on Chronocort®, whatever their randomised treatment, as part of an open-label extension study (to be conducted under a separate protocol). Stress doses of hydrocortisone will be given throughout the study for intercurrent illnesses as medically indicated according to "sick day rules".


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 110 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase III Study of Efficacy, Safety and Tolerability of Chronocort® Compared With Standard Glucocorticoid Replacement Therapy in the Treatment of Congenital Adrenal Hyperplasia
Actual Study Start Date : February 22, 2016
Estimated Primary Completion Date : April 2018
Estimated Study Completion Date : April 2018


Arm Intervention/treatment
Experimental: Chronocort®
Chronocort® will be provided as 5mg, 10mg and 20mg capsules for oral administration. The starting dose for each subject will be based on the subjects previous glucocorticoid therapy dose and then dose titrated to effect.
Drug: Chronocort®
Chronocort® is a patented oral modified release formulation of hydrocortisone which is intended to mimic, or closely match, the serum levels of endogenous cortisol.
Other Name: Hydrocortisone
Active Comparator: standard glucocorticoid therapy
Subjects in this arm will continue previous oral glucocorticoid therapy titrated to effect.
Drug: standard glucocorticoid therapy
Subjects in this arm will continue on their standard hydrocortisone therapy
Other Names:
  • hydrocortisone
  • prednisone
  • prednisolone
  • dexamethasone



Primary Outcome Measures :
  1. Change from baseline in 17-OHP [ Time Frame: 24 weeks ]
    Change from baseline to 24 weeks of the mean of the 24-hour standard deviation score (SDS) profile for 17-OHP.


Secondary Outcome Measures :
  1. Change from baseline in A4 [ Time Frame: 24 weeks ]
    Change from baseline to 24 weeks of the mean of the 24-hour standard deviation score (SDS) profile for A4.

  2. Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [ Time Frame: 24 weeks ]
    AEs will be collected for all subjects from the time of consent up to 30 days ± 3 days following the last visit or, if applicable, the Early Withdrawal visit. Any ongoing AEs post study will be followed to resolution or stabilisation if resolution is not expected. Only treatment emergent AEs will be included in the main safety analysis: other AEs will be listed.

  3. Use and reasons for use of rescue medication [ Time Frame: 24 weeks ]
    The number of times the patients needed rescue medication (supplied as a 'sick day safety pack' plus instructions for use that are called the 'sick days rules') during the study wil be recorded. The reason for the use of the rescue medication will also be recorded.



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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Known CAH due to 21-hydroxylase deficiency (classic CAH) diagnosed in childhood with documented (at any time) elevated 17-OHP and/or A4 and currently treated with hydrocortisone, prednisone, prednisolone or dexamethasone (or a combination of the aforementioned glucocorticoids) on a stable glucocorticoid therapy for a minimum of 6 months.
  2. Provision of signed written informed consent.
  3. Non-pregnant, non-lactating females who are post menopausal, naturally or surgically sterile, or of childbearing potential with a negative urinary pregnancy test and using a medically acceptable method of contraception.
  4. Plasma renin activity (PRA) less than 1.5 times the upper limit of normal (ULN) at screening or within 3 months prior to screening, except in subjects who have been diagnosed with hypertension where the renin is not being used to monitor fludrocortisone replacement.
  5. Plasma renin activity (PRA) less than 1.5 times the upper limit of normal (ULN) at screening or within 3 months prior to screening, except in subjects who have been diagnosed with hypertension where the renin is not being used to monitor fludrocortisone replacement.

Exclusion Criteria:

  1. Co-morbid condition requiring daily administration of a medication (or consumption of any material) that interferes with the metabolism of glucocorticoids.
  2. Clinical or biochemical evidence of hepatic or renal disease. Creatinine over twice the ULN or elevated liver function tests (ALT or AST >2 times the ULN).
  3. Subjects on regular daily inhaled, topical, nasal or oral steroids for any indication other than CAH.
  4. Subjects with any other significant medical or psychiatric conditions that in the opinion of the investigator would preclude participation in the trial.
  5. History of malignancy (other than basal cell carcinoma successfully treated >6 months prior to entry into the study).
  6. Participation in another clinical trial of an investigational or licensed drug or device within the 3 months prior to inclusion in this study.
  7. Subjects with a history of bilateral adrenalectomy.
  8. Subjects having previously been exposed to Chronocort®.
  9. Subjects unable to comply with the requirements of the protocol.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02716818


Contacts
Contact: John Porter, MD info@diurnal.co.uk

Locations
United States, Maryland
National Institutes of Health Clinical Center Recruiting
Bethesda, Maryland, United States, 20892-1932
Principal Investigator: Deborah P Merke, BS MS MD         
Sponsors and Collaborators
Diurnal Limited
Investigators
Principal Investigator: Debbie Merke, MD National Institutes of Health (NIH)

Responsible Party: Diurnal Limited
ClinicalTrials.gov Identifier: NCT02716818     History of Changes
Other Study ID Numbers: DIUR-005
First Posted: March 23, 2016    Key Record Dates
Last Update Posted: July 17, 2017
Last Verified: July 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: To be decided at a later date

Keywords provided by Diurnal Limited:
Glucocorticoid therapy

Additional relevant MeSH terms:
Hyperplasia
Adrenal Hyperplasia, Congenital
Adrenogenital Syndrome
Adrenocortical Hyperfunction
Pathologic Processes
Disorders of Sex Development
Urogenital Abnormalities
Congenital Abnormalities
Genetic Diseases, Inborn
Steroid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Metabolic Diseases
Adrenal Gland Diseases
Endocrine System Diseases
Gonadal Disorders
Hydrocortisone 17-butyrate 21-propionate
Hydrocortisone acetate
Cortisol succinate
Hydrocortisone
Glucocorticoids
Anti-Inflammatory Agents
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs